The present invention relates to the use of certain prostaglandin analogs for the treatment of glaucoma and ocular hypertension. As used herein, the terms "prostaglandin" and "PG" shall refer to prostaglandins and derivatives and analogs thereof, except as otherwise indicated by context.
Naturally-occurring prostaglandins, especially prostaglandins of the F series (such as PGF.sub.2.alpha.), are known to lower intraocular pressure (IOP) after topical ocular instillation, but can cause conjunctival hyperemia and/or edema as well as inflammation. Many synthetic prostaglandins have been observed to lower intraocular pressure, but most such compounds also produce the aforementioned side effects which significantly limit their clinical utility.
Various attempts have been made to overcome these well-known side-effects. Some have synthesized or searched out derivatives of naturally-occurring prostaglandins in an attempt to design out selectively the side effects while maintaining the IOP-lowering effect. See, e.g., Bishop et al. (U.S. Pat. No. 5,510,383) Stjernschantz et al. (U.S. Pat. Nos. 5,422,368, 5,321,128, and 5,296,504), Woodward et al. (U.S. Pat. No. 5,093,329), Chan et al. (WO 92/08465 and U.S. Pat. No. 5,446,041). Others, including Ueno et al. (EP 330 511 A2) and Wheeler (EP 435 682 A2) have tried complexing prostaglandins with various cyclodextrins.
Certain sulfur containing prostaglandin derivatives are known in the art. Glutathione-prostaglandin conjugates and related compounds have been reported in the literature relating to the cytotoxicity of PGA and PGD. See e.g. Cagen, Fales and Pisano, J. Biological Chemistry 251, 6550-54 (1976); Cagen and Pisano, Biochimica et Biophysica Acta 573, 547-51 (1979); Honn and Marnett, Biochemical and Biophysical Research Comn. 129, 34-40 (1985); Atsmon et al., Cancer Res. 50, 1879-85 (1990); Parker and Ankel, Biochemical Pharmacology 43,1053-60 (1992); Ohno, et al., Eicosanoids 5, 81-85 (1992). However, the biological effects of these compounds, other than cytotoxicity or the lack thereof, have not been reported. Stjernschantz et al. (U.S. Pat. No. 5,516,796) disclose ring substituted thioprostaglandins and thioprostagiandin-like compounds for the treatment of glaucoma or ocular hypertension. 7-Thioprostaglandin derivatives may inhibit chemokine-induced cell migration (Kataoka et al. (WO97/01534)) and have been disclosed for the treatment of skin disease (see Hanahima et al. CA Selects: Prostaglandins, 125:185911p (1996)). Also, compounds which are derivatives of 13-thiaprostenoic acid have been reported to lower blood pressure (see, e.g., Radunz et al. (U.S. Pat. No. 4,309,441)).